2-205086880-G-T

Variant names:

• chr2-205086880-G-T
• rs7559302
• NM_001302769.2:c.505-17546G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302769.2(PARD3B):​c.505-17546G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,054 control chromosomes in the GnomAD database, including 5,635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5635 hom., cov: 32)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 5 publications found

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302769.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	NM_001302769.2	MANE Select	c.505-17546G>T		intron	N/A	NP_001289698.1
	PARD3B	NM_152526.6		c.505-17546G>T		intron	N/A	NP_689739.4
	PARD3B	NM_057177.7		c.505-17546G>T		intron	N/A	NP_476518.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	ENST00000406610.7	TSL:1 MANE Select	c.505-17546G>T		intron	N/A	ENSP00000385848.2
	PARD3B	ENST00000358768.6	TSL:1	c.505-17546G>T		intron	N/A	ENSP00000351618.2
	PARD3B	ENST00000351153.5	TSL:1	c.505-17546G>T		intron	N/A	ENSP00000317261.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37488 AN: 151936 Hom.: 5629 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37505 AN: 152054 Hom.: 5635 Cov.: 32 AF XY: 0.247 AC XY: 18326 AN XY: 74322

African (AFR) AF: 0.0725 AC: 3009 AN: 41506

American (AMR) AF: 0.250 AC: 3825 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2012 AN: 5144

South Asian (SAS) AF: 0.205 AC: 990 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3611 AN: 10552

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22273 AN: 67972

Other (OTH) AF: 0.244 AC: 515 AN: 2108

Alfa AF: 0.294 Hom.: 10029

Bravo AF: 0.233

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7559302; hg19: chr2-205951603;